The overall objective of the project is to determine the biochemical interrelationships between the utilization of ketone bodies, glycolysis and amino acid metabolism. This interrelationship is suggested by the recent finding of a newly described syndrome of ketoacidosis which was induced by protein and the reversible inhibition of the glycolysis of the tissue culture (CC-69) cells from this patient. Since there is an increased activity of CoA transferase in rat brain which is correlated with an increased utilization of ketone bodies during the neonatal period, this animal provides an additional system for the study of metabolic interrelationships. The purpose of this proposal is to investigate the utilization of ketones in the fetal, newborn and adult brain, muscle, kidney and heart and to examine the effects of these substrates on glycolysis and amino acid metabolism. Labelled substrate oxidation and utilization, enzyme measurements, and in vivo and in vitro inhibition studies will be utilized in these investigations. Additional studies will investigate the effect of ketosis during pregnancy on these processes. Concurrent studies will also measure these interrelationships in CoA transferase deficient tissue cultured fibroblasts (CC-69) as compared to those in normal controls.